Histone acetylase activity (HAT) of CBP/p300 is believed to be important for their function in transcriptional activation. However, it is not clear what are the real substrates of acetylation by CBP/p300 in vivo, and whether the HAT activity of CBP/p300 is essential for development and tumor suppressor function. To address these issues, I will make a mouse model that expresses a CBP mutant deficient in HAT function (CBP-hat). The phenotypes of heterozygous and homozygous CBP-hat animals will be compared to that of the CBP heterozygous and nullizygous animals to characterize the physiological significance of the HAT function of CBP.